The study aims at identifying protective immune response against severe malaria in young children. This study is based on our earlier studies of pregnancy malaria. Susceptibility to pregnancy malaria (PM) results from the unique binding phenotype of placental parasites that adhere to chondroitin sulfate A (CSA), a molecule that is expressed on the surface of the syncytiotrophoblast and appears throughout the intervillous spaces. Because CSA is not readily accessible for parasite adhesion in the nonpregnant host, women are nave to this parasite subpopulation before their first pregnancy, making first-time mothers most susceptible. Over successive pregnancies women develop specific humoral immunity to placental parasites in the form of anti-adhesion antibodies. Anti-adhesion antibodies are associated with improved pregnancy outcomes. Based on these findings, in the current study we survey the binding phenotype of parasites associated with discrete clinical syndromes collected from children participating in the immune-epi study at Ouelessebougou, Mali, and relate acquisition of anti-adhesion antibodies with protection from severe malaria. An additional aspect of the study includes epidemiological studies to determine the relationship of malaria infection to pregnancy loss and preterm delivery in an area of highly seasonal malaria and the mechanisms that may contribute to these outcomes. During the past fiscal year we have observed that 1. Microscopic and submicroscopic malaria infections during pregnancy increase the likelihood of fetal loss. 2. Preliminary results suggesting that acquired anti-adhesion antibodies are associated with protection from severe malaria. 3. Proteomic data from 15 parasite isolates collected from children with and without severe malaria